This is a request for a Capillary Electrophoresis-Mass Spectrometry (CE- MS) instrument under the Shared Instrumentation Grant mechanism of The National Center for Research Resources. The CE-MS system will be utilized primarily by a major user group comprised of four investigators at The Scripps Research Institute (TSRI) (Drs. Weiss, Henriksen, Gruol and Parsons) and one investigator at the Veterans Administration Medical Center on the campus of UCSD (Dr. Purdy). Each of the investigators in the major user group will use the CE-MS instrument to advance research that is currently funded by NIH awards. There are several characteristics of CE-MS that will accelerate and advance the research of the major user group. First, CE has the ability to separate a wide variety of analytes such as steroids, large and small peptides, oligonucleotides, RNA transcripts and DNA fragments. Second, CE offers unparalleled resolution capabilities and will provide the separation of important analytes with a selectivity that is currently unavailable in our research. The coupling of mass spectrometry (MS) with CE presents a third advantage for using this analytical technique. The combination of the mass/charge (m/z) information and sensitivity provided by MS with the separation characteristics of CE provides a tremendous advance in the unambiguous identification and quantification of biological molecules. Moreover, MS scan spectra can be used for the structural elucidation of novel substances. Finally, the very small sample requirements for CE- MS analyses will enable a substantial reduction in the disturbance made to the physiological systems being monitored, and will increase sample analyte concentrations and improve the time resolution of our measures. These features of CE-MS will advance the research endeavors of the local scientific community in ways that are currently impossible. The CE-MS will be housed in 'core facility' laboratory space at TSRI, and an Internal Advisory Committee will assure the use and equitable sharing of the CE-MS among investigators both within and outside the major user group. This committee is comprised of the Principle Investigator (Dr. Parsons), the Director of the Mass Spectrometry Facility at TSRI (Dr. Siuzdak), a senior researcher with significant CE experience (Dr. Rivier) and the Director of both the Division of Psychopharmacology and the Alcohol Research Center at TSRI (Dr. Koob), organizations with which each of the major users are affiliated. The Senior Vice President of TSRI supports this application, and had agreed that TSRI will assume financial responsibility for the long-term operation and maintenance of the CE- MS.